TY - JOUR
T1 - Phase II clinical trial of fludarabine in chronic lymphocytic leukemia on a weekly low-dose schedule
AU - Kemena, A.
AU - O'brien, S.
AU - Kantarjian, H.
AU - Robertson, L.
AU - Koller, C.
AU - Beran, M.
AU - Estey, E.
AU - Plunkett, W.
AU - Lerner, S.
AU - Keating, M. J.
N1 - Funding Information:
Supported in part by grant CA32839 from the National Cancer Institute, DHHS. Address for correspondence: Michael J. Keating, M.D., Department of Hematology, Box 38, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
PY - 1993
Y1 - 1993
N2 - The major complication during therapy of chronic lymphocytic leukemia (CLL) with the purine nucleotide analogue fludarabine is infection, which is also the main cause of morbidity and mortality in the disease. As the incidence of infectious episodes during therapy correlated with severity of neutropenia, stage of disease, and response to therapy, an effort was made to reduce therapy-related myelosuppression and improve response by altering the conventional therapy regimen. The protocol which yielded a response rate of 57% in previously treated patients with CLL consisted of five consecutive daily doses of 25-30 mg/mz fludarabine given every three to four weeks. Based on observations from intracellular pharmacology studies it was hypothesized that repetitive single weekly doses of fludarabine would allow normal bone marrow cells to recover while maintaining cytotoxic levels in the leukemic cells. The cumulative four-week dose of the once-weekly regimen was approximately 80% of the original protocol. Eleven out of 46 evaluable patients (24% responded to the therapy. Seven patients (15% achieved a complete remission, and four (9% a partial remission. While myelosuppression was reduced by about 30% compared with the original protocol, the incidence of febrile episodes was increased by 17% Pretreatment serum IgG levels below the normal range correlated significantly with a high incidence of infectious episodes and with a short median survival time. These observations suggest that in addition to myelosuppressive therapy, disease related depressed immune function causes morbidity and mortality due to infections. The results further show that changes in the scheduling of the therapy regimen, associated with a slightly lower dose, resulted in reduced efficacy as measured by the response rate.
AB - The major complication during therapy of chronic lymphocytic leukemia (CLL) with the purine nucleotide analogue fludarabine is infection, which is also the main cause of morbidity and mortality in the disease. As the incidence of infectious episodes during therapy correlated with severity of neutropenia, stage of disease, and response to therapy, an effort was made to reduce therapy-related myelosuppression and improve response by altering the conventional therapy regimen. The protocol which yielded a response rate of 57% in previously treated patients with CLL consisted of five consecutive daily doses of 25-30 mg/mz fludarabine given every three to four weeks. Based on observations from intracellular pharmacology studies it was hypothesized that repetitive single weekly doses of fludarabine would allow normal bone marrow cells to recover while maintaining cytotoxic levels in the leukemic cells. The cumulative four-week dose of the once-weekly regimen was approximately 80% of the original protocol. Eleven out of 46 evaluable patients (24% responded to the therapy. Seven patients (15% achieved a complete remission, and four (9% a partial remission. While myelosuppression was reduced by about 30% compared with the original protocol, the incidence of febrile episodes was increased by 17% Pretreatment serum IgG levels below the normal range correlated significantly with a high incidence of infectious episodes and with a short median survival time. These observations suggest that in addition to myelosuppressive therapy, disease related depressed immune function causes morbidity and mortality due to infections. The results further show that changes in the scheduling of the therapy regimen, associated with a slightly lower dose, resulted in reduced efficacy as measured by the response rate.
KW - Chronic lymphocytic leukemia
KW - Fludarabine
KW - Weekly low-dose schedule
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U2 - 10.3109/10428199309145882
DO - 10.3109/10428199309145882
M3 - Article
C2 - 8220117
AN - SCOPUS:0027236732
SN - 1042-8194
VL - 10
SP - 187
EP - 193
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 3
ER -